Pharmaceutics

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9 pages, 1828 KiB

Open AccessArticle

Does Valved Holding Chamber Improve Aerosol Lung Deposition with a Jet Nebulizer? A Randomized Crossover Study

by Luciana Alcoforado, Dulciane Nunes Paiva, Arzu Ari, Jacqueline de Melo Barcelar, Simone Cristina Soares Brandão, James B. Fink and Armele Dornelas de Andrade

Pharmaceutics 2022, 14(3), 566; https://doi.org/10.3390/pharmaceutics14030566 - 4 Mar 2022

Cited by 2 | Viewed by 3349

Abstract

Using valved holding chambers (VHC) during aerosol therapy has been reported to improve the inhaled dose with various aerosol devices, including vibrating mesh nebulizers. The aim of this study was to quantify the pulmonary deposition of a jet nebulizer (JN) with and without [...] Read more.

Using valved holding chambers (VHC) during aerosol therapy has been reported to improve the inhaled dose with various aerosol devices, including vibrating mesh nebulizers. The aim of this study was to quantify the pulmonary deposition of a jet nebulizer (JN) with and without a VHC, and a mesh nebulizer (MN) with a VHC in a randomized cross-over trial with seven healthy consenting adults. Our hypothesis was that the use of a VHC would improve deposition with the JN. Diethylnitriaminopentacetic acid with technetium (DTPA-Tc99m), with the activity of 1 mC with 0.9% saline solution was nebulized. The radiolabeled aerosol was detected by 2D planar scintigraphy after administration. The pulmonary deposition was greater with a JN with a VHC (4.5%) than a JN alone (3.2%; p = 0.005. However, an MN with a VHC (30.0%) was six-fold greater than a JN or JN with a VHC (p < 0.001). The extrapulmonary deposition was higher in the JN group without a VHC than in the other two modalities (p < 0.001). Deposition in the device was greater with a JN + VHC than an MN+/VHC (p < 0.001). Lower residual drug at the end of the dose was detected with an MN than either JN configuration. The exhaled dose was greater with a JN alone than either an MN or JN with VHC (p < 0.001). In conclusion, the addition of the VHC did not substantially improve the efficiency of aerosol lung deposition over a JN alone. Full article

(This article belongs to the Special Issue Medical Aerosol Drug Delivery)

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13 pages, 4739 KiB

Open AccessArticle

Reconciling Oxygen and Aerosol Delivery with a Hood on In Vitro Infant and Paediatric Models

by Shu-Hsin Chen, Hsiu-Chu Chang, Ming-Yi Chien, Jinxiang Xi and Hui-Ling Lin

Pharmaceutics 2022, 14(1), 91; https://doi.org/10.3390/pharmaceutics14010091 - 31 Dec 2021

Cited by 2 | Viewed by 1816

Abstract

This study aimed to evaluate optimal aerosol and oxygen delivery with a hood on an infant model and a paediatric model. A facemask and a hood with three inlets, with or without a front cover, were used. A small-volume nebuliser with a unit-dose [...] Read more.

This study aimed to evaluate optimal aerosol and oxygen delivery with a hood on an infant model and a paediatric model. A facemask and a hood with three inlets, with or without a front cover, were used. A small-volume nebuliser with a unit-dose of salbutamol was used for drug delivery and an air entrainment nebuliser was used to deliver oxygen at 35%. Infant and paediatric breathing patterns were mimicked; a bacterial filter was connected to the end of a manikin trachea for aerosol drug collection, and an oxygen analyser was used to measure the oxygen concentration. For the infant model, inhaled drug dose was significantly higher when the nebuliser was placed in the back of the hood and with a front cover. This was verified by complementary computational simulations in a comparable infant-hood model. For the paediatric model, the inhaled dose was greater with a facemask than with a hood. Oxygen delivery with a facemask and a hood with a front cover achieved a set concentration in both models, yet a hood without a front cover delivered oxygen at far lower concentrations than the set concentration. Full article

(This article belongs to the Special Issue Medical Aerosol Drug Delivery)

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23 pages, 7790 KiB

Open AccessArticle

Advanced Microparticulate/Nanoparticulate Respirable Dry Powders of a Selective RhoA/Rho Kinase (Rock) Inhibitor for Targeted Pulmonary Inhalation Aerosol Delivery

by Priya Muralidharan, Don Hayes, Jr., Jeffrey R. Fineman, Stephen M. Black and Heidi M. Mansour

Pharmaceutics 2021, 13(12), 2188; https://doi.org/10.3390/pharmaceutics13122188 - 17 Dec 2021

Cited by 6 | Viewed by 4035

Abstract

Pulmonary hypertension (PH) is a progressive disease that eventually leads to heart failure and potentially death for some patients. There are many unique advantages to treating pulmonary diseases directly and non-invasively by inhalation aerosols and dry powder inhalers (DPIs) possess additional unique advantages. [...] Read more.

Pulmonary hypertension (PH) is a progressive disease that eventually leads to heart failure and potentially death for some patients. There are many unique advantages to treating pulmonary diseases directly and non-invasively by inhalation aerosols and dry powder inhalers (DPIs) possess additional unique advantages. There continues to be significant unmet medical needs in the effective treatment of PH that target the underlying mechanisms. To date, there is no FDA-approved DPI indicated for the treatment of PH. Fasudil is a novel RhoA/Rho kinase (ROCK) inhibitor that has shown great potential in effectively treating pulmonary hypertension. This systematic study is the first to report on the design and development of DPI formulations comprised of respirable nanoparticles/microparticles using particle engineering design by advanced spray drying. In addition, comprehensive physicochemical characterization, in vitro aerosol aerosol dispersion performance with different types of human DPI devices, in vitro cell-drug dose response cell viability of different human respiratory cells from distinct lung regions, and in vitro transepithelial electrical resistance (TEER) as air-interface culture (AIC) demonstrated that these innovative DPI fasudil formulations are safe on human lung cells and have high aerosol dispersion performance properties. Full article

(This article belongs to the Special Issue Medical Aerosol Drug Delivery)

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11 pages, 1382 KiB

Open AccessArticle

Deposition of Inhaled Levofloxacin in Cystic Fibrosis Lungs Assessed by Functional Respiratory Imaging

by Carsten Schwarz, Claudio Procaccianti, Benjamin Mignot, Hosein Sadafi, Nicolas Schwenck, Xabier Murgia and Federico Bianco

Pharmaceutics 2021, 13(12), 2051; https://doi.org/10.3390/pharmaceutics13122051 - 1 Dec 2021

Cited by 5 | Viewed by 2414

Abstract

Pulmonary infections caused by Pseudomonas aeruginosa (PA) represent the leading cause of pulmonary morbidity in adults with cystic fibrosis (CF). In addition to tobramycin, colistin, and aztreonam, levofloxacin has been approved in Europe to treat PA infections. Nevertheless, no lung deposition data on [...] Read more.

Pulmonary infections caused by Pseudomonas aeruginosa (PA) represent the leading cause of pulmonary morbidity in adults with cystic fibrosis (CF). In addition to tobramycin, colistin, and aztreonam, levofloxacin has been approved in Europe to treat PA infections. Nevertheless, no lung deposition data on inhaled levofloxacin are yet available. We conducted a Functional Respiratory Imaging (FRI) study to predict the lung deposition of levofloxacin in the lungs of patients with CF. Three-dimensional airway models were digitally reconstructed from twenty high-resolution computed tomography scans obtained from historical patients’ records. Levofloxacin aerosols generated with the corresponding approved nebuliser were characterised according to pharmacopeia. The obtained data were used to inform a computational fluid dynamics simulation of levofloxacin lung deposition using breathing patterns averaged from actual CF patients’ spirometry data. Levofloxacin deposition in the lung periphery was significantly reduced by breathing patterns with low inspiratory times and high inspiratory flow rates. The intrathoracic levofloxacin deposition percentages for moderate and mild CF lungs were, respectively, 37.0% ± 13.6 and 39.5% ± 12.9 of the nominal dose. A significant albeit modest correlation was found between the central-to-peripheral deposition (C/P) ratio of levofloxacin and FEV₁. FRI analysis also detected structural differences between mild and moderate CF airways. FRI revealed a significant intrathoracic deposition of levofloxacin aerosols, which distributed preferentially to the lower lung lobes, with an influence of the deterioration of FEV₁ on the C/P ratio. The three-dimensional rendering of CF airways also detected structural differences between the airways of patients with mild and moderate CF. Full article

(This article belongs to the Special Issue Medical Aerosol Drug Delivery)

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23 pages, 2226 KiB

Open AccessArticle

Targeting of Inhaled Therapeutics to the Small Airways: Nanoleucine Carrier Formulations

by Danforth P. Miller, Thomas E. Tarara and Jeffry G. Weers

Pharmaceutics 2021, 13(11), 1855; https://doi.org/10.3390/pharmaceutics13111855 - 3 Nov 2021

Cited by 7 | Viewed by 3075

Abstract

Current dry powder formulations for inhalation deposit a large fraction of their emitted dose in the upper respiratory tract where they contribute to off-target adverse effects and variability in lung delivery. The purpose of the current study is to design a new formulation [...] Read more.

Current dry powder formulations for inhalation deposit a large fraction of their emitted dose in the upper respiratory tract where they contribute to off-target adverse effects and variability in lung delivery. The purpose of the current study is to design a new formulation concept that more effectively targets inhaled dry powders to the large and small airways. The formulations are based on adhesive mixtures of drug nanoparticles and nanoleucine carrier particles prepared by spray drying of a co-suspension of leucine and drug particles from a nonsolvent. The physicochemical and aerosol properties of the resulting formulations are presented. The formulations achieve 93% lung delivery in the Alberta Idealized Throat model that is independent of inspiratory flow rate and relative humidity. Largely eliminating URT deposition with a particle size larger than solution pMDIs is expected to improve delivery to the large and small airways, while minimizing alveolar deposition and particle exhalation. Full article

(This article belongs to the Special Issue Medical Aerosol Drug Delivery)

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13 pages, 2728 KiB

Open AccessArticle

Bronchodilator Delivery via High-Flow Nasal Cannula: A Randomized Controlled Trial to Compare the Effects of Gas Flows

by Jie Li, Yibing Chen, Stephan Ehrmann, Jie Wu, Lixin Xie and James B Fink

Pharmaceutics 2021, 13(10), 1655; https://doi.org/10.3390/pharmaceutics13101655 - 11 Oct 2021

Cited by 9 | Viewed by 2805

Abstract

(1) Background: Aerosol delivery via high-flow nasal cannula (HFNC) has attracted increasing clinical interest. In vitro studies report that the ratio of HFNC gas flow to patient inspiratory flow (GF:IF) is a key factor in the efficiency of trans-nasal aerosol delivery. (2) Methods: [...] Read more.

(1) Background: Aerosol delivery via high-flow nasal cannula (HFNC) has attracted increasing clinical interest. In vitro studies report that the ratio of HFNC gas flow to patient inspiratory flow (GF:IF) is a key factor in the efficiency of trans-nasal aerosol delivery. (2) Methods: In a randomized controlled trial, patients with a history of COPD or asthma and documented positive responses to inhaled bronchodilators in an outpatient pulmonary function laboratory were recruited. Subjects were randomized to receive inhalation at gas flow ratio settings of: GF:IF = 0.5, GF:IF = 1.0, or GF = 50 L/min. Subjects were assigned to inhale saline (control) followed by salbutamol via HFNC with cumulative doses of 0.5 mg, 1.5 mg, 3.5 mg, and 7.5 mg. Spirometry was performed at baseline and 10–12 min after each inhalation. (3) Results: 75 subjects (49 asthma and 26 COPD) demonstrating bronchodilator response were enrolled. Per the robust ATS/ERS criteria no difference was observed between flows, however using the criteria of post-bronchodilator forced expiratory volume in the first second (FEV₁) reaching the screening post-bronchodilator FEV₁ with salbutamol, a higher percentage of subjects receiving GF:IF = 0.5 met the criteria at a cumulative dose of 1.5 mg than those receiving GF:IF = 1.0, and GF = 50 L/min (64% vs. 29% vs. 27%, respectively, p = 0.011). Similarly at 3.5 mg (88% vs. 54% vs. 46%, respectively, p = 0.005). The effective dose at GF:IF = 0.5 was 1.5 mg while for GF = 50 L/min it was 3.5 mg. (4) Conclusions: During salbutamol delivery via HFNC, cumulative doses of 1.5 mg to 3.5 mg resulted in effective bronchodilation. Applying the robust ATS/ERS criteria no difference was observed between the flows, however using the more sensitive criteria of subjects reaching post screening FEV₁ to salbutamol via HFNC, a higher number of subjects responded to the doses of 0.5 mg and 1.5 mg when HFNC gas flow was set at 50% of patient peak inspiratory flow. Full article

(This article belongs to the Special Issue Medical Aerosol Drug Delivery)

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15 pages, 2801 KiB

Open AccessArticle

Physiologic Effects of Instilled and Aerosolized Surfactant Using a Breath-Synchronized Nebulizer on Surfactant-Deficient Rabbits

by Robert M. DiBlasi, Kellie J. Micheletti, Joseph D. Zimmerman, Jonathan A. Poli, James B. Fink and Masaki Kajimoto

Pharmaceutics 2021, 13(10), 1580; https://doi.org/10.3390/pharmaceutics13101580 - 29 Sep 2021

Cited by 9 | Viewed by 2819

Abstract

Surfactant administration incorporates liquid bolus instillation via endotracheal tube catheter and use of a mechanical ventilator. Aerosolized surfactant has generated interest and conflicting data related to dose requirements and efficacy. We hypothesized that aerosolized surfactant with a novel breath-actuated vibrating mesh nebulizer would [...] Read more.

Surfactant administration incorporates liquid bolus instillation via endotracheal tube catheter and use of a mechanical ventilator. Aerosolized surfactant has generated interest and conflicting data related to dose requirements and efficacy. We hypothesized that aerosolized surfactant with a novel breath-actuated vibrating mesh nebulizer would have similar efficacy and safety as instilled surfactant. Juvenile rabbits (1.50 ± 0.20 kg, n = 17) were sedated, anesthetized, intubated, and surfactant was depleted via lung lavage on mechanical ventilation. Subjects were randomized to receive standard dose liquid instillation via catheter (n = 5); low dose surfactant (n = 5) and standard dose surfactant (n = 5) via aerosol; and descriptive controls (no treatment, n = 2). Peridosing events, disease severity and gas exchange, were recorded every 30 min for 3 h following surfactant administration. Direct-Instillation group had higher incidence for peridosing events than aerosol. Standard dose liquid and aerosol groups had greater PaO₂ from pre-treatment baseline following surfactant (p < 0.05) with greater ventilation efficiency with aerosol (p < 0.05). Our study showed similar improvement in oxygenation response with greater ventilation efficiency with aerosol than liquid bolus administration at the same dose with fewer peridosing events. Breath-synchronized aerosol via nebulizer has potential as a safe, effective, and economical alternative to bolus liquid surfactant instillation. Full article

(This article belongs to the Special Issue Medical Aerosol Drug Delivery)

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16 pages, 2601 KiB

Open AccessArticle

Evaluation of Aerosol Drug Delivery Options during Adult Mechanical Ventilation in the COVID-19 Era

by Piers J. Naughton, Mary Joyce, Marc Mac Giolla Eain, Andrew O’Sullivan and Ronan MacLoughlin

Pharmaceutics 2021, 13(10), 1574; https://doi.org/10.3390/pharmaceutics13101574 - 28 Sep 2021

Cited by 15 | Viewed by 4607

Abstract

Drug delivery devices used for aerosol therapy during mechanical ventilation to ease the symptoms of respiratory diseases provide beneficial treatment but can also pose challenges. Reflecting the significant changes in global guidance around aerosol usage and lung-protective ventilation strategies, seen in response to [...] Read more.

Drug delivery devices used for aerosol therapy during mechanical ventilation to ease the symptoms of respiratory diseases provide beneficial treatment but can also pose challenges. Reflecting the significant changes in global guidance around aerosol usage and lung-protective ventilation strategies, seen in response to the COVID-19 pandemic, for the first time, we describe the drug delivery performance of commonly used devices under these conditions. Here, vibrating mesh nebuliser (VMN), jet nebuliser (JN) and pressurised metered-dose inhaler (pMDI) performance was assessed during simulated adult mechanical ventilation. Both standard test breathing patterns and those representatives of low tidal volume (LTV) ventilation with concurrent active and passive humidification were investigated. Drug delivery using a VMN was significantly greater than that with a JN and pMDI for both standard and LTV ventilation. Humidification type did not affect the delivered dose across all device types for standard ventilation. Significant variability in the pMDI dosing was evident, depending on the timing of actuation and the adapter type used. pMDI actuation synchronised with inspiration resulted in a higher delivered drug dose. The type of adapter used for pMDI actuation influenced drug delivery, with the highest dose observed using the CombiHaler. Full article

(This article belongs to the Special Issue Medical Aerosol Drug Delivery)

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9 pages, 1397 KiB

Open AccessArticle

Quantifying Delivered Dose with Jet and Mesh Nebulizers during Spontaneous Breathing, Noninvasive Ventilation, and Mechanical Ventilation in a Simulated Pediatric Lung Model with Exhaled Humidity

by Arzu Ari and James B. Fink

Pharmaceutics 2021, 13(8), 1179; https://doi.org/10.3390/pharmaceutics13081179 - 30 Jul 2021

Cited by 2 | Viewed by 4312

Abstract

Acutely ill children may transition between spontaneous breathing (SB), noninvasive ventilation (NIV), and mechanical ventilation (MV), and commonly receive the same drug dosage with each type of ventilatory support and interface. This study aims to determine the aerosol deposition with jet (JN) and [...] Read more.

Acutely ill children may transition between spontaneous breathing (SB), noninvasive ventilation (NIV), and mechanical ventilation (MV), and commonly receive the same drug dosage with each type of ventilatory support and interface. This study aims to determine the aerosol deposition with jet (JN) and mesh nebulizers (MN) during SB, NIV, and MV using a pediatric lung model. Drug delivery with JN (Mistymax10) and MN (Aerogen Solo) was compared during SB, NIV, and MV using three different lung models set to simulate the same breathing parameters (Vt 250 mL, RR 20 bpm, I:E ratio 1:3). A heated humidifier was placed between the filter and test lung to simulate exhaled humidity (35 ± 2 °C, 100% RH) with all lung models. Albuterol sulfate (2.5 mg/3 mL) was delivered, and the drug deposited on an absolute filter was eluted and analyzed with spectrophotometry. Aerosol delivery with JN was not significantly different during MV, NIV, and SB (p = 0.075), while inhaled dose obtained with MN during MV was greater than NIV and SB (p = 0.001). The delivery efficiency of MN was up to 3-fold more than JN during MV (p = 0.008), NIV (p = 0.005), and SB (p = 0.009). Delivered dose with JN was similar during MV, NIV, and SB, although the delivery efficiency of MN differs with different modes of ventilation. Full article

(This article belongs to the Special Issue Medical Aerosol Drug Delivery)

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8 pages, 1412 KiB

Open AccessArticle

Nebuliser Type Influences Both Patient-Derived Bioaerosol Emissions and Ventilation Parameters during Mechanical Ventilation

by Mary Joyce, James A. McGrath, Marc Mac Giolla Eain, Andrew O’Sullivan, Miriam Byrne and Ronan MacLoughlin

Pharmaceutics 2021, 13(2), 199; https://doi.org/10.3390/pharmaceutics13020199 - 2 Feb 2021

Cited by 21 | Viewed by 3182

Abstract

COVID-19 may lead to serious respiratory complications which may necessitate ventilatory support. There is concern surrounding potential release of patient-derived bioaerosol during nebuliser drug refill, which could impact the health of caregivers. Consequently, mesh nebulisers have been recommended by various clinical practice guidelines. [...] Read more.

COVID-19 may lead to serious respiratory complications which may necessitate ventilatory support. There is concern surrounding potential release of patient-derived bioaerosol during nebuliser drug refill, which could impact the health of caregivers. Consequently, mesh nebulisers have been recommended by various clinical practice guidelines. Currently, there is a lack of empirical data describing the potential for release of patient-derived bioaerosol during drug refill. This study examined the release of simulated patient-derived bioaerosol, and the effect on positive end expiratory pressure during nebuliser refill during mechanical ventilation of a simulated patient. During jet nebuliser refill, the positive end expiratory pressure decreased from 4.5 to 0 cm H₂O. No loss in pressure was noted during vibrating mesh nebuliser refill. A median particle number concentration of 710 particles cm⁻³ above ambient was detected when refilling the jet nebuliser in comparison to no increase above ambient detected when using the vibrating mesh nebuliser. The jet nebuliser with the endotracheal tube clamped resulted in 60 particles cm⁻³ above ambient levels. This study confirms that choice of nebuliser impacts both the potential for patient-derived bioaerosol release and the ability to maintain ventilator circuit pressures and validates the recommended use of mesh nebulisers during mechanical ventilation. Full article

(This article belongs to the Special Issue Medical Aerosol Drug Delivery)

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10 pages, 633 KiB

Open AccessArticle

Effect of Tiotropium Soft Mist Inhalers on Dynamic Changes in Lung Mechanics of Patients with Chronic Obstructive Pulmonary Disease Receiving Mechanical Ventilation: A Prospective Pilot Study

by Pin-Kuei Fu, Yu-Feng Wei, Chau-Chyun Sheu, Chen-Yu Wang, Chi-Kuei Hsu, Chia-Min Chen, Wei-Chih Chen and Kuang-Yao Yang

Pharmaceutics 2021, 13(1), 51; https://doi.org/10.3390/pharmaceutics13010051 - 31 Dec 2020

Cited by 2 | Viewed by 2801

Abstract

The effects of tiotropium bromide soft mist inhalers (SMIs) in patients with chronic obstructive pulmonary disease (COPD) receiving mechanical ventilation remain unexplored. This study investigated the dynamic effects of a tiotropium SMI on lung mechanics and gas exchange in these patients. We analyzed [...] Read more.

The effects of tiotropium bromide soft mist inhalers (SMIs) in patients with chronic obstructive pulmonary disease (COPD) receiving mechanical ventilation remain unexplored. This study investigated the dynamic effects of a tiotropium SMI on lung mechanics and gas exchange in these patients. We analyzed 11 mechanically ventilated and hemodynamically stable patients with COPD who experienced acute exacerbation and were ready to be weaned from the ventilator. Two puffs of tiotropium (2.5 μg/puff) were administered with a T-adaptor connected to the ventilator circuit. Lung mechanics—peak inspiratory pressure, plateau pressure, mean airway pressure, maximum respiratory resistance (Rrs), and gas exchange function—were analyzed. The two-puff tiotropium SMI treatment led to the greatest reduction in Rrs at 6 h, with the Rrs returning to baseline gradually, and significantly improved the PaO₂/FiO₂ ratio at 24 h. Compared with baseline values, tiotropium SMI had the strongest effect on Rrs between hours 3 and 6 but did not significantly affect hemodynamic parameters. Tiotropium SMI administration in mechanically ventilated patients with COPD achieved the greatest reduction in Rrs at 6 h and significantly improved the PaO₂/FiO₂ ratio at 24 h. Future studies should investigate whether the bronchodilation effect can be improved with increased dosage or frequency. Full article

(This article belongs to the Special Issue Medical Aerosol Drug Delivery)

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9 pages, 1170 KiB

Open AccessArticle

In Vitro Evaluation of a Vibrating-Mesh Nebulizer Repeatedly Use over 28 Days

by Hui-Ling Lin, Chi-Shuo Chen, James B. Fink, Guo-Hao Lee, Chun-Wei Huang, Jui-Chi Chen and Zi Yi Chiang

Pharmaceutics 2020, 12(10), 971; https://doi.org/10.3390/pharmaceutics12100971 - 15 Oct 2020

Cited by 15 | Viewed by 4075

Abstract

This in vitro study evaluates the performance of a disposable vibrating-mesh nebulizer when used for 28 days. A lung model was used to simulate the breathing pattern of an adult with chronic obstructive pulmonary disease. The vibrating-mesh nebulizer was used for three treatments/day [...] Read more.

This in vitro study evaluates the performance of a disposable vibrating-mesh nebulizer when used for 28 days. A lung model was used to simulate the breathing pattern of an adult with chronic obstructive pulmonary disease. The vibrating-mesh nebulizer was used for three treatments/day over 28 days without cleaning after each test. Results showed that the inhaled drug dose was similar during four weeks of use (p = 0.157), with 16.73 ± 4.46% at baseline and 15.29 ± 2.45%, 16.21 ± 2.21%, 17.56 ± 1.98%, and 17.13 ± 1.81%, after the first, second, third, and fourth weeks, respectively. The particle size distribution, residual drug volume, and nebulization time remained similar across four weeks of use (p = 0.110, p = 0.763, and p = 0.573, respectively). Mesh was inspected using optical microscopy and showed that approximately 50% of mesh pores were obscured after 84 runs, and light penetration through the aperture plate was significantly reduced after the 21st use (p < 0.001) with no correlation to nebulizer performance. We conclude that the vibrating-mesh nebulizer delivered doses of salbutamol solution effectively over four weeks without cleaning after each use even though the patency and clarity of the aperture plate were reduced by the first week of use. Full article

(This article belongs to the Special Issue Medical Aerosol Drug Delivery)

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